Myeloma in mice and man is detectable when the immunoglobulin class produced by the tumor is elevated above the normal serum immunoglobulin level or when the tumor is manifested in vivo. The MOPC 104E murine myeloma is unique in that it produces a tumor specific circulating marker (IgM(lambda)) that permits tumor detection even in the presence of normal levels of all classes of serum immunoglobulins and allows quantitation of normally undetectable tumor clones. MOPC 104E myeloma specific IgM(lambda) anti-dextran continue to circulate in animals apparently cured by chemotherapy. The cells in this state are defined as representing a "clinically stable tumor clone" (CSTC). Since IgM(lambda) anti-dextran is a specific marker produced only by the original tumor, we shall use it a) to determine if CSTC remain stable or relapse as the animals age, b) to establish the mechanism of control in vivo as to whether the immune system or another mode of tumor control is operating and c) to test the concept that the destruction of the tumor cell number to a critical plateau level is sufficient to contain the remaining neoplastc cells. The existence of low levels of myeloma proteins and indolent forms of unequivocal multiple myeloma has been established. It is also known that in some patients after chemotherapy the myeloma protein reaches a plateau phase and in some instances the clinical status becomes stabilized for many years. These studies are significant in that they imply when the tumor cell numbers are reduced in the host, without further treatment, the host automatically and specifically assumes control of the remaining clones of tumor cells. Understanding the mechanism operating in the host which allows each individual to naturally control his own myeloma clones would be a significant advance over the current methods now available.